Dermatoses produce a great burden of suffering on the afflicted. The number of inflammatory or allergic dermatoses is continuously increasing, especially in the industrialized countries. Common manifestations of dermatoses include contact dermatitis and atopic dermatitis.
Contact dermatitis is an acute or chronic inflammation, often sharply demarcated, produced by substances in contact with the skin. Contact dermatitis may be caused by a primary chemical irritant or may be a delayed hypersensitivity reaction. Contact dermatitis ranges from transient redness to severe swelling with bulla formation; itching and vesiculation are common. Any exposed skin surface that contacts a sensitizing or irritating substance may be involved. Thus, dermatitis may be due to an airborne substance (e.g., ragweed pollen, insecticide spray). Typically, the dermatitis is first sharply limited to the site of contact; later it may spread.
Products for the treatment of these disorders include antihistaminics or glucocorticoids. For prophylaxis, on the other hand, no suitable preparations are known. Unless the offending agent is removed, treatment may be ineffective or the dermatitis may promptly recur. Patients with photoallergic or phototoxic contact dermatitis should also avoid exposure to light. Antihistamines (except for their sedative effect) and allergen desensitization are ineffective in contact dermatitis.
Atopic dermatitis is a chronic, itching, superficial inflammation of the skin, frequently associated with a personal or family history of related disorders (e.g., hay fever, asthma). Atopic dermatitis is a chronic inflammatory skin disorder. According to data from a national screening survey of dermatologic disease, the prevalence of atopic dermatitis among persons one year to 74 years of age ranges form seven to 24 cases per 1,000.
Atopic dermatitis is most prevalent in infancy and childhood and tends to be less prevalent during puberty; however, the condition often persists into adulthood, and in a small number of cases (fewer than two percent), onset occurs in persons order than 45 years. Atopic dermatitis is not a primary allergic disorder per se but appears to be inherited in association with certain allergic disorders. Environmental stimuli can trigger the disease in genetically predisposed individuals.
The increased prevalence of atopic dermatitis in the 1990s has been attributed to environmental irritants, infections, previous exposure to allergenic foods, and airborne allergens such as dust, mites, animal dander, and pollens.
Atopy is characterized by physiologic, immunopathologic, and pharmacological abnormalities that involve the skin. These abnormalities include (1) a lowered threshold to itch stimuli, (2) a hypersensitivity to alpha-adrenergic agonists and to cholinergic agents, which may result from partial beta-adrenergic blockade, (3) a very dry (xerotic), hyperkeratotic skin, which has decreased water-holding capacity, (4) a marked tendency to produce lichenification in response to friction and scratching, and (5) a tendency for the skin to be heavily colonized with bacteria, especially pathogenic staphylococci.
Itching is the primary symptom of atopic dermatitis. The pruritus may be generalized or localized, especially to the flexor surfaces. It fluctuates seasonally, is often worse in the wintertime, and has a diurnal rhythm in which itching is minimal at midday and maximal in the evening. Higher body temperature and capillary dilatation in the evening and the absence of daytime distractions account for the diurnal cycle. Emotional stress can also provoke and aggravate itching and scratching.
The diagnosis of atopic dermatitis is usually clinically evident; histologic examination reveals a nonspecific eczematous process. Patients commonly have a history of dermatitis in infancy and a family or personal history of atopy. Eczema connotes a reaction pattern of the skin to multiple exogenous and endogenous stimuli that is characteristic of a particular type of dermatitis. At some stage of the eczematous process, small, often microscopic, blisters or vesicles from within the epidermis because of accumulation of intercellular fluid, also called spongiosis.
The objectives of local therapy for atopic dermatitis are suppression of inflammation, hydration of the skin, reduction of skin bacteria, and prevention of itching and scratching. Itching leads to scratching and to trauma of the skin, resulting in infection, lichenification, and eczematization.
Anti-inflammatory and antipuritic agents include topical corticosteroids of varying potencies and purified coal tar derivatives such as five percent liquor carbonis detergens (LCD) in a propylene glycol or cream base.
However, these therapies, have some disadvantages; in many people, some antihistaminics cause languor and drowsiness. Permanent use of glucocorticoids (for example cortisone) is usually unjustifiable for medical reasons owing to many unpleasant side effects. The same also applies to most so-called NSAID (non-steroidal anti-inflammatory drugs).
Research in the area of allergic reactions of the lung has provided evidence that arachidonic acid derivatives formed by the action of lipoxygenases are related to various disease states. Some of these arachidonic acid metabolites have been classified as members of a family of eicosatetraenoic acids termed leukotrienes. Three of these substances are currently thought to be major components of what has been previously called slow reacting substance of anaphylaxis (SRS-A) and have been designated leukotrienes C.sub.4, D.sub.4, and E.sub.4 (LTC.sub.4, LTD.sub.4, and LTE.sub.4, respectively).
Another arachidonic acid metabolite, leukotriene B.sub.4 (LTB.sub.4), is a proinflammatory lipid which has been implicated in the pathogenesis of psoriasis, arthritis, chronic lung diseases, acute respiratory distress syndrome, shock, asthma, inflammatory bowel diseases, and other inflammatory states characterized by the infiltration and activation of polymorphonuclear leukocytes and other proinflammatory cells. Thus activated, the polymorphonuclear leukocytes liberate tissue-degrading enzymes and reactive chemicals causing the inflammation. Antagonism of LTB.sub.4 should therefore provide a novel therapeutic approach to treatment of these and other LTB.sub.4 mediated conditions. Activated microglial cells are the central nervous system analogues of systemic proinflammatory cells.
Because of the debilitating effects of dermatoses there continues to exist a need for effective treatments.